Este artigo é um Preprint
Preprints são relatos preliminares de pesquisa que não foram certificados pela revisão por pares. Eles não devem ser considerados para orientar a prática clínica ou comportamentos relacionados à saúde e não devem ser publicados na mídia como informação estabelecida.
Preprints publicados online permitem que os autores recebam feedback rápido, e toda a comunidade científica pode avaliar o trabalho independentemente e responder adequadamente. Estes comentários são publicados juntamente com os preprints para qualquer pessoa ler e servir como uma avaliação pós-publicação.
Intestinal organoids expose heterogeneity in SARS-CoV-2 susceptibility
Preprint
em En
| PREPRINT-BIORXIV
| ID: ppbiorxiv-452680
ABSTRACT
Gastrointestinal effects associated with COVID-19 are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine inter-individual variability. Infection of intestinal organoids derived from different donors with SARS-CoV-2 resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with ACE2 expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue indicating this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.
cc_no
Texto completo:
1
Coleções:
09-preprints
Base de dados:
PREPRINT-BIORXIV
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Preprint